Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome.
Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome.
复制标题
DOI：
10.1016/s1083-8791(99)70006-6
复制
发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
McDonald, G B
中科院分区：
文献类型：
--
作者：
Lee, J L;Gooley, T;McDonald, G B
本研究的目的是确定高剂量布苏凡、美伐兰和硫替帕治疗后静脉闭塞性疾病（VOD）的发生率以及导致更严重结果的危险因素。我们对253例恶性疾病患者进行了连续随访，这些患者在干细胞收获后接受了自体移植，随后使用了12mg /kg布苏凡、100mg /m2美伐兰和500mg /m2硫替帕。VOD的诊断是基于体重增加、肝肿大和黄疸。使用逻辑回归模型确定中度或重度点播的危险因素。253例患者中有70例（28%）发生VOD，其中31例（12%）为中度VOD， 11例（4%）为重度VOD。高胆红素血症的中位发病天数为第9天，明显晚于环磷酰胺方案后黄疸的发病时间（p < 0.001）。70例VOD患者中有23例体重增加和黄疸消退，数周后再次出现，这是一个不良预后迹象。中度或重度VOD的危险因素为淋巴瘤或骨髓瘤（与乳腺癌的比值比为2.65）、肿瘤累及肝脏（比值比为3.95）、移植前一个月发热（比值比为3.32）和既往放射治疗（比值比为2.70）。我们得出的结论是，与以往以环磷酰胺为基础的治疗方案相比，布苏凡、美法兰和硫替帕治疗后的VOD发生频率和严重程度较低，且发生时间较晚。重要的危险因素包括除乳腺癌以外的诊断、肝转移、持续发热和既往放射治疗。本研究表明，总毒性相当的烷基化剂的肝毒性不同。
The purpose of this study was to determine the incidence of veno-occlusive disease (VOD) after a high-dose regimen of busulfan, melphalan, and thiotepa and the risk factors for a more severe outcome. We followed 253 consecutive patients with malignant disorders who received autologous transplants after stem cell harvest followed by 12 mg/kg busulfan, 100 mg/m2 melphalan, and 500 mg/m2 thiotepa. Diagnosis of VOD was based on weight gain, hepatomegaly, and jaundice. Risk factors for moderate or severe VOD were identified using logistic regression models. VOD occurred in 70 of 253 patients (28%), of whom 31 (12%) had moderate and 11 (4%) severe VOD. The median day of onset of hyperbilirubinemia was day 9, significantly later than the onset of jaundice after our cyclophosphamide-based regimens (p < 0.001). Resolution of weight gain and jaundice, followed by their reappearance several weeks later, occurred in 23 of 70 patients with VOD and was an adverse prognostic sign. Risk factors for moderate or severe VOD were a diagnosis of lymphoma or myeloma (odds ratio [OR] 2.65 compared with breast cancer), tumor involvement in the liver (OR 3.95), fever in the month before transplant (OR 3.32), and prior radiation therapy (OR 2.70). We conclude that VOD after busulfan, melphalan, and thiotepa was less frequent and less severe and developed later than VOD after our historical cyclophosphamide-based regimens. Significant risk factors included a diagnosis other than breast cancer, hepatic metastases, persistent fever, and prior radiation therapy. This study suggests that alkylating agents of comparable overall toxicity differ in their liver toxicity.